Abstract
Retinal ischemia is a common pathomechanism in many ocular disorders such as age-related macular degeneration (AMD), diabetic retinopathy, glaucoma or retinal vascular occlusion. Several studies demonstrated that ischemia/reperfusion (I/R) leads to morphological and functional changes of different retinal cell types. However, little is known about the ischemic effects on the optic nerve. The goal of this study was to evaluate these effects. Ischemia was induced by raising the intraocular pressure (IOP) in one eye of rats to 140 mmHg for 1 h followed by natural reperfusion. After 21 days, histological as well as quantitative real-time PCR (qRT-PCR) analyses of optic nerves were performed. Ischemic optic nerves showed an infiltration of cells and also degeneration with signs of demyelination. Furthermore, a migration and an activation of microglia could be observed histologically as well as on mRNA level. In regard to macroglia, a trend toward gliosis could be noted after ischemia induction by vimentin staining. Additionally, an up-regulation of glial fibrillary acidic protein (GFAP) mRNA was found in ischemic optic nerves. Counting of oligodendrocyte transcription factor 2 positive (Olig2+) cells revealed a decrease of oligodendrocytes in the ischemic group. Also, myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) mRNA expression was down-regulated after induction of I/R. On immunohistological level, a decrease of MOG was detectable in ischemic optic nerves as well. In addition, SMI-32 stained neurofilaments of longitudinal optic nerve sections showed a strong structural damage of the ischemic optic nerves in comparison to controls. Consequently, retinal ischemia impacts optic nerve degeneration. These findings could help to better understand the course of destruction in the optic nerve after an ischemic insult. Especially for therapeutic studies, the optic nerve is important because of its susceptibility to be damaged as a result to retinal ischemic injury and also its connecting function between the eye and the brain. So, future drug screenings should target not only the retina, but also the functionality and structure of the optic nerve. In the future, these results could lead to the development of new therapeutic strategies for treatment of ischemic injury.
Highlights
Ischemia plays an important role in various retinal diseases, including age-related macular degeneration (AMD), diabetic retinopathy, glaucoma and retinal vein occlusion
There, the cells were arranged in a row via toluidine blue staining, bright areas could be recognized in the ischemic optic nerves, which indicate a demyelination
It still needs to be clarified if the ischemic damage overlaps from the retina to the optic nerve or whether a second initial damage is set in the optic nerve head (ONH) by ischemia induction
Summary
Ischemia plays an important role in various retinal diseases, including age-related macular degeneration (AMD), diabetic retinopathy, glaucoma and retinal vein occlusion These diseases are leading causes of blindness worldwide (Cai et al, 2015). Due to the renewed oxygen supply a higher concentration of the reactive oxygen species ensues, which triggers the formation of free radicals These radicals attack the cell structure and proteins and cause additional massive tissue damage (Szabo et al, 1991; Belforte et al, 2011). Regarding the optic nerve investigation, these immune cells are of interest Due to their ability to perform antigen presentation and elimination of cell debris by phagocytosis, invading microglia serves as indicators for early tissue damage and play an essential role in initiation and resumption of de- and remyelination (Voss et al, 2012). A functional loss of the inner retinal cell layers could be measured in previous studies by full-field flash electroretinography 21 days after I/R induction (Schmid et al, 2014)
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